Tiêu chuẩn iso 13408 5 2006

C035290e book INTERNATIONAL STANDARD ISO 13408 5 First edition 2006 11 15 Reference number ISO 13408 5 2006(E) © ISO 2006 Aseptic processing of health care products — Part 5 Sterilization in place Tra[.]

STANDARD

ISO 13408-5

First edition2006-11-15

Reference numberISO 13408-5:2006(E)

Aseptic processing of health care

products —

Part 5:

Sterilization in place

Traitement aseptique des produits de santé —

Partie 5: Stérilisation sur place

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ISO 13408-5:2006(E)

1 Scope 1

2 Normative references 1

3 Terms and definitions 2

4 Quality system elements 3

4.1 General 3

4.2 Management responsibility 3

4.3 Design control 3

4.4 Measuring instruments and measuring systems 3

5 Process and equipment characterization 4

5.1 General concepts 4

5.2 Effectiveness of sterilization in place (SIP) 4

5.3 Equipment 4

6 Sterilizing agent characterization 6

6.1 Selection of sterilizing agent(s) 6

6.2 Quality of sterilizing agent(s) 6

6.3 Safety and the environment 6

7 SIP process 6

7.1 Process parameters 6

7.2 Cycle development 7

8 Validation 7

8.1 Validation protocol 7

8.2 Design qualification 7

8.3 Installation qualification 7

8.4 Operational qualification 8

8.5 Performance qualification 8

8.6 Review and approval of validation 10

8.7 Requalification 10

9 Routine monitoring and control 10

9.1 SIP process control 10

9.2 Procedures 10

9.3 SIP process records 11

9.4 Change control 11

9.5 Maintenance of equipment 11

10 Personnel training 11

Annex A (informative) Steam sterilization in place 12

Bibliography 14

International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.The main task of technical committees is to prepare International Standards Draft International Standardsadopted by the technical committees are circulated to the member bodies for voting Publication as anInternational Standard requires approval by at least 75 % of the member bodies casting a vote.

Attention is drawn to the possibility that some of the elements of this document may be the subject of patentrights ISO shall not be held responsible for identifying any or all such patent rights

ISO 13408-5 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products

ISO 13408 consists of the following parts, under the general title Aseptic processing of health care products:

— Part 1: General requirements

— Part 2: Filtration

— Part 3: Lyophilization

— Part 4: Clean-in-place technologies

— Part 5: Sterilization in place

— Part 6: Isolator systems

ISO 13408-5:2006(E)

Introduction

During the process of preparing ISO 13408-1, several items, e.g filtration, freeze drying and sterilization inplace, were found to be in need of supplementary information which was too voluminous to be given incorresponding annexes

This part of ISO 13408 includes requirements and guidance that are to be observed during sterilization in place.The purpose of this part of ISO 13408 is to achieve standardization in the field of validation and routine control

of sterilization in place processes used in the manufacture of health care products

Sterilization in place is, in most instances, preceded by cleaning in place which is described in ISO 13408-4.While methods of cleaning in place and sterilization in place differ considerably in technology, the concept of insitu treatment is similar

The most important issue to consider in establishing sterilization-in-place technology is the design of thesystem(s) to ensure that they be able to successfully sterilize manufacturing equipment to the desired level ofsterility assurance

INTERNATIONAL STANDARD ISO 13408-5:2006(E)

Aseptic processing of health care products —

NOTE SIP can be achieved by using steam or other gaseous or liquid sterilizing agents Specific guidance on steamsterilization in place, which is the most common method used, is given in Annex A

1.2 This part of ISO 13408 applies to processes where sterilizing agents are delivered to the internal surfaces

of equipment that can come in contact with the product

1.3 This part of ISO 13408 does not apply to processes where equipment is dismantled and delivered to asterilizer

1.4 This part of ISO 13408 does not supersede or replace national regulatory requirements, such as GoodManufacturing Practices (GMPs) and/or compendial requirements that pertain in particular national or regionaljurisdictions

1.5 This part of ISO 13408 does not specify requirements for development, validation and routine control of aprocess for inactivating the causative agents of spongiform encephalopathies, such as scrapie, bovinespongiform encephalopathy and Creutzfeldt-Jakob disease Specific recommendations have been produced inparticular countries for the processing of materials potentially contaminated with these agents

NOTE See also ISO 22442-1, ISO 22442-2 and ISO 22442-3

2 Normative references

The following referenced documents are indispensable for the application of this document For datedreferences, only the edition cited applies For undated references, the latest edition of the referenced document(including any amendments) applies

ISO 11138 (all parts), Sterilization of health care products — Biological indicators

ISO 11140 (all parts), Sterilization of health care products — Chemical indicators

ISO 13408-1, Aseptic processing of health care products — Part 1: General requirements

ISO 13408-4, Aseptic processing of health care products — Part 4: Clean-in-place technologies

ISO 14161, Sterilization of health care products — Biological indicators — Guidance for the selection, use andinterpretation of results

ISO 14937, Sterilization of health care products — General requirements for characterization of a sterilizingagent and the development, validation and routine control of a sterilization process for medical devices

ISO 13408-5:2006(E)

ISO 17665-1, Sterilization of health care products — Moist heat — Part 1: Requirements for the development,validation and routine control of a sterilization process for medical devices

ISO/IEC 90003, Software engineering — Guidelines for the application of ISO 9001:2000 to computer software

3 Terms and definitions

For the purposes of this document, the terms and definitions given in ISO 13408-1 and the following apply

specified value for a process variable

NOTE The specification for a sterilization process includes the process parameters and their tolerances

[ISO/TS 11139:2006, definition 2.34]

3.5

process variable

condition within a sterilization process, changes in which alter microbicidal effectiveness

EXAMPLE Time, temperature, pressure, concentration, humidity, wavelength

to as “Steam SIP”

ISO 13408-5:2006(E)

3.7

sterility assurance level

SAL

probability of a single viable microorganism occurring on an item after sterilization

NOTE 1 The term SAL takes a quantitative value, generally or When applying this quantitative value toassurance of sterility, an SAL of provides a greater assurance of sterility than an SAL of

4.1.1 The requirements of ISO 13408-1 shall apply.

4.1.2 Documented procedures for each phase of the development, validation, routine monitoring and control of

the SIP process shall be prepared and implemented

4.1.3 Documents required by this part of ISO 13408 shall be reviewed and approved by designated personnel 4.1.4 Records of development, validation, routine control and monitoring shall be maintained to provide

evidence of conformity to the requirements of this part of ISO 13408

4.2 Management responsibility

4.2.1 The responsibilities and authority for implementing and performing the procedures described in this part

of ISO 13408 shall be specified

4.2.2 If the requirements of this part of ISO 13408 are undertaken by organizations with separate quality

management systems, the responsibilities and authority of each party shall be specified

4.3 Design control

Characterization of the sterilizing agent, sterilization process, equipment to deliver SIP and equipment to besubject to SIP shall be undertaken in accordance with a documented plan At defined stages, design reviewsshall be planned, conducted and documented

4.4 Measuring instruments and measuring systems

4.4.1 A documented system shall be specified for the calibration of all measuring instruments or measuring

ISO 13408-5:2006(E)

4.4.2 The accuracy and tolerance of the measuring instrument shall be adequate to the process to be

measured

5 Process and equipment characterization

5.1 General concepts

5.1.1 Specifications for the SIP process shall include, but not be limited to:

a) compatibility of the equipment with the sterilizing agent(s) and processing conditions;

b) pre-requisite cleaning procedure, where necessary;

c) introduction, homogeneity, distribution and contact time with the sterilizing agent;

d) physical and/or chemical characteristics of sterilizing agent(s);

e) demonstration of the efficacy of the process;

f) sterilizing agent residuals or degradation products;

g) drying of product contact surfaces, where necessary;

h) maintenance of sterility after the completion of the process;

i) acceptable tolerances for any potential residues from the process in the product to be made in theequipment;

j) physical integrity testing and establishing limits

5.1.2 Process parameters and their tolerances shall be specified, documented and reviewed.

5.1.3 During production processes, the sterilizing conditions achieved shall be monitored, maintained within

specified tolerances, and documented throughout the duration of the sterilization process

5.1.4 Although the entire processing system can be sterilized as a single entity in SIP, it can be advantageous

to divide the system into several parts in order to simplify the sterilization procedures When a large system issterilized by dividing it into several segments, the segments should overlap to ensure that all portions of thesystem are adequately and effectively sterilized

5.1.5 Complex sequences of opening and shutting of valves in the pipes of a system could be required Where

this is controlled manually, detailed documentation of individual steps is required Where automation is used,electronic automation systems should be carefully designed and validated

5.2 Effectiveness of sterilization in place (SIP)

The sterility assurance level of the process shall be established and documented Justification of the processparameters shall be included in the documentation

5.3 Equipment

5.3.1 Equipment to be subjected to SIP

5.3.1.1 The equipment shall be designed and manufactured to facilitate SIP and to ensure that the sterilizing

agent(s) can enter all internal product contact parts of the equipment to be sterilized (such as filter housings,pipe branches, and valves)

Design considerations shall include, but not be limited to:

a) smoothness of inner surface of equipment;

b) accessibility of the sterilizing agent to all relevant surfaces;

ISO 13408-5:2006(E)

c) correct placement of ports to admit the sterilizing agent(s) and, where applicable, to allow bleeding tofacilitate sterilizing agent distribution;

d) absence of dead legs in piping systems;

e) drainability of the system (e.g slope of piping to ensure the complete removal of remaining liquid in thesystem);

f) correct placement of ports to permit inclusion of process monitoring devices;

g) where applicable, exhaust port for safe removal of gaseous sterilizing agent;

h) where applicable, resistance of the equipment to pressure, vacuum and heat;

i) compatibility of materials of construction (e.g pipes, tanks, valves, nozzles, filters, gaskets, sensors) withthe sterilizing agent, over the anticipated number of sterilization cycles;

j) provisions for maintenance of sterility during and after completion of SIP (e.g by elevated pressure).Materials made of resin, such as gaskets, require particular attention

Inner corners or shoulders of the tank and/or vessel of the system should be designed so that they do not entrapair and thereby cause incomplete sterilization in the resulting air pocket

Valves, connections and other equipment (such as heat exchangers) should be designed and oriented toreduce the inaccessible surfaces and entrapment of air

5.3.1.2 Specification of the equipment shall include, but not be limited to:

a) physical description of the equipment, together with any necessary ancillary items (including materials ofconstruction and “as-built” drawings);

b) specifications of the sterilizing agent and means by which it is provided, including any additives orprecursors necessary for its delivery;

c) description of instrumentation for monitoring and controlling the sterilization process, including sensorcharacteristics and their locations, indicating instruments and recording instruments;

NOTE Temperature monitoring will normally be at the slowest-to-heat locations

d) description of safety features, including those for personnel and environmental protection;

e) description of installation requirements, if applicable;

f) documented evidence that the software used to control and/or monitor the process is prepared inaccordance with a quality system and that the software meets its design intention;

g) a process flow diagram that outlines the processing equipment layout to be sterilized, including valvesequencing

5.3.2 Equipment to be used for SIP

5.3.2.1 The equipment shall be designed and manufactured to effectively perform and control SIP of the

equipment to be sterilized Its primary functions to be verified in qualification shall include but not be limited to:a) generation of the sterilizing agent, where applicable;

b) admittance of the sterilizing agent into the equipment to be sterilized in a controlled and safe manner;c) distribution of the sterilizing agent within the equipment to be sterilized;

d) maintenance of effective sterilization conditions throughout the equipment to be sterilized;

e) controlling and monitoring of the sterilization conditions in the defined locations;

f) safe removal of the sterilizing agent;

g) maintenance of the sterility of the equipment

ISO 13408-5:2006(E)

5.3.2.2 Specification of the equipment shall include at least:

a) a physical description of the equipment, together with any necessary ancillary items, including materials ofconstruction and “as-built” drawings;

b) a specification of the sterilizing agent and means by which it is provided, including any additives orprecursors necessary for its delivery;

c) a description of instrumentation for monitoring, controlling and recording the sterilization process, includingsensor characteristics, tolerances and locations;

d) a description of safety features, including those for personnel and environmental protection;

e) a description of installation requirements, if applicable; this should include the location and the environment

in which the equipment is to be installed and the services that are required for SIP and for the area in whichthe SIP system is installed;

f) documented evidence that the software used to control and/or monitor the process is prepared inaccordance with a quality system and that the software meets its design intention

6 Sterilizing agent characterization

6.1 Selection of sterilizing agent(s)

6.1.1 The sterilizing agent used shall be compatible with the equipment, shall not leave objectionable residues

and shall be capable of delivering the stated sterility assurance level within specified sterilization parameters

6.1.2 In selecting sterilizing agents, due consideration should be given to the potential for interactions with

product residue (see ISO 13408-4)

6.2 Quality of sterilizing agent(s)

6.2.1 Data shall be available to demonstrate the microbicidal effectiveness of the sterilizing agent.

6.2.2 A specification including purity for the sterilizing agent shall be established and documented.

6.3 Safety and the environment

6.3.1 A material safety data sheet or analogous safety information for the sterilizing agent shall be available 6.3.2 An assessment of the potential environmental impact shall be available for any sterilizing agent other

than steam

7 SIP process

7.1 Process parameters

7.1.1 Process parameters as justified in 5.2, including their minimum and maximum limits, shall be defined and

documented Process parameters shall be adequate to ensure sterilization of the equipment being subjected toSIP